Novel CYP4F22 mutations associated with autosomal recessive congenital ichthyosis (ARCI). Study of the CYP4F22 c.1303C>T founder mutation

Abstract

Mutations in CYP4F22 cause autosomal recessive congenital ichthyosis (ARCI). However, less than 10% of all ARCI patients carry a mutation in CYP4F22. In order to identify the molecular basis of ARCI among our patients (a cohort of ninety-two Spanish individuals) we performed a mutational analysis using direct Sanger sequencing in combination with a multigene targeted NGS panel. From these, eight ARCI families (three of them with Moroccan origin) were found to carry five different CYP4F22 mutations, of which two were novel. Computational analysis showed that the mutations found were present in highly conserved residues of the protein and may affect its structure and function. Seven of the eight families were carriers of a highly recurrent CYP4F22 variant, c.1303C>T; p.(His435Tyr). A 12Mb haplotype was reconstructed in all c.1303C>T carriers by genotyping ten microsatellite markers flanking the CYP4F22 gene. A prevalent 2.52Mb haplotype was observed among Spanish carrier patients suggesting a recent common ancestor. A smaller core haplotype of 1.2Mb was shared by Spanish and Moroccan families. Different approaches were applied to estimate the time to the most recent common ancestor (TMRCA) of carrier patients with Spanish origin. The age of the mutation was calculated by using DMLE and BDMC2. The algorithms estimated that the c.1303C>T variant arose approximately 2925 to 4925 years ago, while Spanish carrier families derived from a common ancestor who lived in the XIII century. The present study reports five CYP4F22 mutations, two of them novel, increasing the number of CYP4F22 mutations currently listed. Additionally, our results suggest that the recurrent c.1303C>T change has a founder effect in Spanish population and c.1303C>T carrier families originated from a single ancestor with probable African ancestry.

CYP4F22-Related Autosomal Recessive Congenital Ichthyosis: Clinical Presentation

“…In the US, the prevalence of ARCI has been reported to be 1:200,000-300,000 [ 2 ]. ARCI is associated with mutations in various genes, including ABCA12, ALOX12B, ALOXE3, CYP4F22, NIPAL4, TGM1, CERS3, PNPLA1, CASP14, SDR9C7, AND SULT2B1 [ 3 ]. Most of these identified genes participate in the synthesis of enzymes and transporters involved in the construction, transport, and/or assembly of components of the stratum corneum [ 4 ].…”

Successful Treatment of an Adult with Atopic Dermatitis and Lamellar Ichthyosis Using Dupilumab

“…Furthermore, other genes associated with LI include ALOX12B, ALOXE3, NIPAL4, CYP4F22, and ABCA12 . 10 …”

A case of self-healing collodion baby

“…oMóWienie Termin rybia łuska pochodzi od greckiego słowa ichthys (ryba) i odnosi się do podobieństwa wyglądu group of keratinisation disorders and usually cover the entire or most of the skin [1,6].…”

“…Doniesienia o rybiej łusce znane są w literaturze indyjskiej i chińskiej od kilkuset lat. Ichtiozy stanowią część dużej, klinicznie i etiologicznie niejednorodnej grupy zaburzeń rogowacenia i zazwyczaj obejmują całą lub większą część skóry [1,6].…”